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1. EU Law Restitution Revisited: In Search of Lost Criteria

Author

Magnus Strand

Subjects
EU law, Restituition, Member State liability, Criteria, Recovery of unlawful charges, Labor market. Labor supply. Labor demand, HD5701-6000.9, Law, Business, HF5001-6182
Abstract

Since Francovich it seems the damages remedy has become The Remedy for individuals suffering economic loss by reason of EU law infringements by Member States. There is however an alternative to damages in private enforcement of EU law, in fact an antecedent to Francovich: Restitution by reason of a breach of EU law. Nonetheless, the criteria for restitution from a Member State, by reason of its breach of WU law, still remain neglected in comparison to the close attention and debates surrounding the criteria for the damages action against Member State. The purpose of this contribution is thus to identify and to discuss the distinctive elements of restitution as a remedy in the event of a breach of EU law by a Member State. Focus is on the very criteria that constitute legal basis for a claim of restitution from a Member State under EU law and the extent to which those criteria should be governed by EU law or by national law. Less attention is devoted to exceptions from liability to make restitution, although their existence in the case law is duly noted. The criteria identified in the case law are (1) the existence of a substantive right conferred on the claimant by EU law, (2) the existence of a payment from the claimant, collect by or on behalf of Member State, (3) the incompatibility of the basis of that payment with EU law, and ((4) that the payment follows as an inevitable consequence of the breach of EU law by the Member State. Case law hints on the more precise legal content of the criteria are examined in an attempt to shed light on their proper interpretation and application. It is noted that the second and the third criteria cannot, on the basis of existing case law, be defined with precision. In that connection it is discussed whether the second criterion should be subdivided into two criteria: Impoverishment of the claimant and enrichment of the Member State. As regards to the fourth criterion it is noted that it is uncertain whether it applies at all. Finally it is submitted that some of the difficulties could be overcome if the Court of Justice were to distinguish clear cases of repayment of charges levied by a Member State institution or agency in breach of EU law from more difficult cases of possible liability by reason of the enrichment of Member States.

Published
2017
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2. Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women.

Author

Therése Andersson, Kotryna Simonyte, Ruth Andrew, Magnus Strand, Jonas Burén, Brian R Walker, Cecilia Mattsson, and Tommy Olsson

Subjects
Medicine, Science
Abstract

With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol)/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P

Published
2009
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6. Investment Firms, Accountability, and the Effective Rule of Law

Author

Magnus Strand and Carl Fredrik Bergström

Abstract

This chapter presents how the results of this book’s study confirm that there are a wide range of legal mechanisms for accountability within the regulatory framework on markets in financial instruments, and that some of these are more visible than others. It also demonstrates the crucial and sometimes novel role of investment firms: how such firms can be held accountable, but also hold EU agencies and national authorities to account for their actions or, indeed, appear in a dual role in a private law context. The chapter then considers the implications of these findings for EU law and the EU legal system. It also addresses how the findings contribute to the understanding of the concept of legal accountability in EU law, introducing the notion of an ‘infrastructure’ for accountability. The notion of an ‘infrastructure’ for accountability is a theoretical tool that is helpful to explain how the rule of law in the EU can be kept efficient by promoting and maintaining clear and precise pathways for accountability.

Published
2021
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7. Damages Liability as a Dual Opportunity to Promote Accountability

Author

Magnus Strand

Abstract

This chapter examines the dual role of investment firms in accountability through damages claims. It begins by looking at the opportunities to promote accountability for the investment firms themselves, focusing on the relevant passage in MiFID II (Article 69(2)(3)) and the conditions to be satisfied. The chapter then considers the opportunities for investment firms to act as agents for the rule of law by holding EU and national authorities accountable through actions for damages. The underlying theory in this presentation is that damages liability can contribute to accountability, and thereby to deterrence from infringements of MiFID II and MiFIR. Consequently, the chapter argues that damages liability should be promoted as an instrument of the rule of law in the financial markets.

Published
2021
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8. The Passing-On Problem in Damages and Restitution Under EU Law : Second Edition

Author

Magnus Strand, Ignacio García-Perrote Martínez, Magnus Strand, and Ignacio García-Perrote Martínez

Subjects
Damages--European Union countries
Abstract

‘Passing-on'occurs when harm or loss incurred by a business is passed on to burden that business's customers or the next level of the supply chain. In this thoroughly revised and updated second edition, the authors provide the only available comprehensive examination of passing-on in damages and restitution under EU law. The analysis covers a broad range of contexts including competition damages and the repayment of charges.The book offers a systematic examination of the key questions facing parties in a passing-on situation: When can downstream claimants bring an action? How can claimants demonstrate sufficient proximity to the original harmful act or unjustified transaction? Will the possibility of passing-on be relevant to the estimation of the award? These questions are assessed for actions against the EU, a Member State and private individuals.Key Features:A specific focus on EU law and guidance that will be relevant to lawyers throughout the EUA multi-faceted and fully contextualised analysis of the defence of passing-on and the position of potential claimants downstream in the supply chainPractical suggestions for consistent approaches to passing-on in EU law across existing and future contextsExtensive updates comprising new case law and materials across all contexts examinedAn expansion of discussions to encompass crucial new developments since the first edition of the bookThis magisterial work is an invaluable point of reference for practitioners working in damages and restitution law, but also in other fields of commercial law, including competition law and consumer law. Legislators and policy-makers in the EU and beyond will also benefit from the lucid analysis of the various policy choices made in the EU and US.

Published
2023

9. On the Choice of Uniform or Personalized Prices in the Digital Economy : Spatial Price Policy in Two-Sided Markets

Author

Eidhamar, Eirik, Helberg, Magnus Strand, and Kind, Hans Jarle

Subjects
economics, economic analysis
Abstract

In this thesis, we examine firms’ choice of price policy, uniform or personalized prices, in the digital economy. We focus on firms operating in the digital economy as the prevalence of big data allows firms in this industry the opportunity to apply personalized pricing. We survey relevant literature on product differentiation, two-sided markets and first-degree price discrimination in spatial models. Further, we propose a Hotelling model of a twosided market consisting of symmetric firms, consumers and advertisers. The firms choose their pricing policies, invest in product quality and set the prices in the advertiser and consumer market. To our knowledge, the model is the first of its kind to combine the choice of price policy, the presence of a two-sided market and quality investments in the same framework. We present two versions of the model, a one-sided duopoly model and a two-sided duopoly model. In the one-sided model we find that the firms will always choose to price discriminate as it constitutes a dominant strategy, complementing the early literature on the field. In contrast, we show that in the two-sided model with an adequately large advertiser market, the optimal price policy strategy is characterized by a mixed strategy. Thus, the firms will not always choose to price discriminate with the introduction of an advertiser market. For the firms, a large advertisement market drives costly quality investments. This has implications on the choice of price policy as pricing uniformly softens the competition in quality relative to personalized pricing. nhhmas

Published
2021

10. Legal Accountability in EU Markets for Financial Instruments : The Dual Role of Investment Firms

Author

Carl Fredrik Bergström, Magnus Strand, Carl Fredrik Bergström, and Magnus Strand

Subjects
Mutual funds--European Union countries, Liability (Law)--European Union countries, Financial instruments--European Union countries
Abstract

The proper functioning of the EU financial market is protected by public actors - both national and supranational - responsible for rulemaking and supervision of investment firms and other private actors. At the same time the effectiveness of the EU legal system requires vigilance from private actors such as investment firms but also their clients, invoking their rights before national authorities and courts. This means that investment firms have a dual role within the system, turning them into subjects of control and enforcement but also agents in the maintenance of the rule of law. Legal Accountability in EU Markets for Financial Instruments brings together a group of scholars with expertise from different legal disciplines but a shared interest for the EU internal market and the way it develops. It integrates a modern study of the form and function of EU rulemaking in the internal market after the financial crisis. The book includes an evaluation of core aspects of rulemaking in the financial market and that way provides a cross-cutting treatment of EU law. The focus of the book is set on the regulatory framework in MiFIDII and MiFIR and thematic questions around legal mechanisms for accountability and the role of investment firms in the operation of those mechanisms. It further discusses the implications for EU law and the EU legal system and gives readers a thorough understanding of the concept of accountability through its own findings.

Published
2021

11. EU och civilrättens splittring: Exemplet preskriptionoch ränta vid skadestånd

Author

Magnus Strand

Subjects
Political science, Civil law (legal system), General Engineering, Private law, Religious studies
Abstract

Debatten om civilrattens splittring har accentuerats genom de nordiska landernas intrade i EU respektive EES. I artikeln illustreras detta med de nya reglerna om preskription och ranta vid skadestand pa grund av en overtradelse av konkurrensratten. Genom ett exempel visas hur den nya regleringen markant okar det totala ersattningsbeloppet. Den nyligen inforda sarregleringen kritiseras eftersom den skapar en omotiverad olikabehandling av rattssystematiskt sett liknande situationer. Som alternativ foreslas en samlad egen reglering av preskription och ranta for fordringar om skadestand, och en enhetlig behandling av de fall dar den skadelidande svavar i okunskap om sin skada. Artikeln lamnar ocksa vissa, om an allmant hallna, forslag till hur vi i den nordiska rattsgemenskapen kan varna var civilratts konsekvens och systematik samtidigt som vi uppfyller vara EU-rattsliga eller EES-rattsliga skyldigheter.

Published
2017
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13. The choice of instrument for EU legislation: mapping the system of governance under MiFID II and MiFIR

Author

Magnus Strand

Subjects
Centralisation, Character (mathematics), General level, Political science, Corporate governance, Legislation, Legislature, Public administration
Abstract

This study was designed to explore the level and character of EU centralisation through the legal instruments MiFID II and MiFIR. The conclusion is that at a general level the choice of legislative ...

Published
2020
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24. EU Competition Litigation : Transposition and First Experiences of the New Regime

Author

Magnus Strand, Vladimir Bastidas, Marios C Iacovides, Magnus Strand, Vladimir Bastidas, and Marios C Iacovides

Subjects
Actions and defenses--European Union countries--Congresses, Antitrust law--European Union countries--Congresses, International and municipal law--European Union countries--Congresses, Damages--European Union countries--Congresses
Abstract

All EU Member States have now transposed Directive 2014/104/EU on damages actions for breaches of competition law into national law. The Directive (and the soft-law instruments accompanying it) not only marks a new phase for private enforcement of competition law but also, more generally, provides a novel and thought provoking instance of EU harmonisation of aspects of private law and civil litigation.Following up on a previous volume in the Swedish Studies in European Law series, published in 2016, this book offers contributions from top practitioners and scholars from all over Europe, who present and discuss first experiences from the implementation of the new damages regime in various jurisdictions.Topics covered include theoretical and practical reflections on the state of private enforcement in Europe, the balancing of conflicting interests pertaining to public and private enforcement of competition law respectively, and specific legal issues such as causation and the estimation of harm. The authors explore problems solved, problems created, and future challenges in the new regime of private enforcement of competition law in Europe, offering predictions as to issues that may have to be settled through recourse to the European Court of Justice.

Published
2019

26. Passing-on unlawful charges : still no small matter

Author

Magnus Strand and Erik Monsen

Subjects
Harmonization of national laws, Repayment of charges, EU law, Tax law, Law, Restitution, Passing-on
Abstract

This contribution focuses on the so-called passing-on problem in actions for repayment of charges levied by Member States in breach of EU law. ‘Passing-on’ occurs when the economic burden of a charge levied from a business is passed on to burden that business’ customers, and possibly even further down the supply chain. The main issues at stake in the passing-on problem are whether actual or possible passing-on should be relevant to the amount repayable, and whether (and against whom) downstream claimants should be able to bring an action in respect of an economic burden passed on to them. Using examples from their home jurisdictions Sweden and Norway, the authors demonstrate that the passing-on problem is a multi-million euro issue which remains governed by diverging national laws, albeit subject to some restrictions developed by the Court of Justice in the absence of EU harmonization. With a view to safeguarding legal certainty, the effective protection of EU law rights, and the elimination of random discrepancies among national rules that are crucial to the proper functioning of the internal market, the authors call for EU harmonization of the legal issues triggered by passing-on. To that end, the authors present two alternative models for harmonization.

Published
2019

29. The Passing-On Problem in Damages and Restitution Under EU Law

Author

Magnus Strand and Magnus Strand

Subjects
Damages--European Union countries, Third parties (Law)--European Union countries
Abstract

Passing-on'occurs when harm or loss incurred by a business is passed on to burden that business's customers or the next level of the supply chain. In this authoritative book Magnus Strand provides the first comprehensive examination of passing-on in EU law damages and restitution. The analysis covers a broad range of contexts including competition damages and the repayment of charges. The book offers a systematic examination of the key questions facing parties in a passing-on situation: When can downstream claimants bring an action? How can claimants demonstrate sufficient proximity to the original harmful act or unjustified transaction? Will a possibility of passing-on be relevant to the estimation of the award? These questions are assessed for actions against the EU, a Member State and private individuals. Key features of this book include: • specific EU law focus and guidance that will be relevant to lawyers throughout the EU • a multi-faceted analysis of the defence of passing-on and the position of potential claimants downstream in the supply chain • practical suggestions for consistent approaches to passing-on in EU law across existing and future contexts. This timely work will be an invaluable point of reference for practitioners working in damages and restitution law, but also in other fields of commercial law, including competition law and consumer law. Legislators and policy-makers in the EU and beyond will also benefit from the lucid analysis of the various policy choices made in the EU and US.

Published
2017

30. Genetic algorithm-based re-optimization of the Schrock catalyst for dinitrogen fixation

Author

Magnus Strandgaard, Julius Seumer, Bardi Benediktsson, Arghya Bhowmik, Tejs Vegge, and Jan H. Jensen

Subjects
de novo discovery, Physical and theoretical chemistry, QD450-801
Abstract

This study leverages a graph-based genetic algorithm (GB-GA) for the design of efficient nitrogen-fixing catalysts as alternatives to the Schrock catalyst, with the aim to improve the energetics of key reaction steps. Despite the abundance of nitrogen in the atmosphere, it remains largely inaccessible due to its inert nature. The Schrock catalyst, a molybdenum-based complex, offered a breakthrough but its practical application is limited due to low turnover numbers and energetic bottlenecks. The genetic algorithm in our study explores the chemical space for viable modifications of the Schrock catalyst, evaluating each modified catalyst’s fitness based on reaction energies of key catalytic steps and synthetic accessibility. Through a series of selection and optimization processes, we obtained fully converged catalytic cycles for 20 molecules at the B3LYP level of theory. From these results, we identified three promising molecules, each demonstrating unique advantages in different aspects of the catalytic cycle. This study offers valuable insights into the potential of generative models for catalyst design. Our results can help guide future work on catalyst discovery for the challenging nitrogen fixation process.

Published
2023
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31. Indirect Purchasers, Passing-on and the New Directive on Competition Law Damages

Author

Magnus Strand

Subjects
medicine.medical_specialty, Public law, Law, Economics, Econometrics and Finance (miscellaneous), medicine, Damages, Private law, Business, Competition law, Directive, Civil law (common law)
Abstract

This article aims to report and to analyse the approach chosen in the upcoming directive on damages for a breach of competition law, and accompanying instruments, to the position of indirect purcha ...

Published
2014
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32. Harmonising EU Competition Litigation : The New Directive and Beyond

Author

Maria Bergström, Marios Iacovides, Magnus Strand, Maria Bergström, Marios Iacovides, and Magnus Strand

Subjects
International and municipal law--European Union countries--Congresses, Antitrust law--European Union countries--Congresses, Damages--European Union countries--Congresses
Abstract

This volume in the Swedish Studies in European Law series, produced by the Swedish Network for European Legal Studies, heralds the new harmonised regime of private enforcement of EU competition law. In 2013, the Commission issued a Communication and Practical Guide to the quantification of harm in antitrust litigation and a Recommendation on collective redress. In 2014, the long-awaited Directive on actions for damages for infringements of EU competition law was finally adopted. In 2016, the Commission is expected to issue guidelines on the passing-on of overcharges. This book examines these recent developments and offers the perspectives of judges, officials, practitioners and academics. With a preface by Judge Carl Wetter of the General Court, the book explores five different themes. In section one, the main policy issues and challenges are presented. In section two, the new regime is placed in the bigger picture of recent EU law developments. In section three, the nexus between private enforcement and transparency is investigated. A comparative perspective is offered in section four by looking into private enforcement in five Member State jurisdictions. Finally, issues relating to causation, harm and indirect purchasers are explored in section five.

Published
2016

34. Maternal Foxp3 Expressing CD4+ CD25+ and CD4+ CD25− Regulatory T-Cell Populations are Enriched in Human Early Normal Pregnancy Decidua: A Phenotypic Study of Paired Decidual and Peripheral Blood Samples

Author

Lucia Mincheva-Nilsson, Tanya Dimova, Olga Nagaeva, Malin Hedlund, Lennart Kjellberg, Magnus Strand, Eva Dehlin, and Ann-Christin Stenqvist

Subjects
Fetus, Pregnancy, Regulatory T cell, medicine.medical_treatment, Immunology, Decidua, Obstetrics and Gynecology, FOXP3, Immunosuppression, biochemical phenomena, metabolism, and nutrition, Biology, medicine.disease, Phenotype, medicine.anatomical_structure, Reproductive Medicine, Antigen, medicine, Immunology and Allergy
Abstract

PROBLEM: Regulatory T cells (Treg cells), a small subset of CD4(+) T cells maintaining tolerance by immunosuppression, are proposed contributors to the survival of the fetal semiallograft. We inves ...

Published
2011
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36. Third International Stroke Summit

Author

Tae-Hee Cho, Rina Torisu, Christine Roffe, G. Cesana, F. Vancheri, Elisa Giorli, Jung Im Seok, Marc Hermier, Shahram Oveisgharan, Nizal Sarrafzadegan, Seung Soo Sheen, Allan Hackshaw, Seung Hyeon Yeo, Kotaro Yasumori, Takahiro Nakano, Hiroki Ohkuma, Karel Fuentes, Jean-Claude Froment, Diosely C. Silveira, Nikolaos I.H. Papamitsakis, Shahin Shirani, Kwang Ho Lee, Shidokht Hosseini, Elizabeth Cheek, Sheila Sills, Yves Berthezène, Sandeep Gupta, Oh Young Bang, L. Palmieri, Chin Sang Chung, Stefan Söderberg, Noriko Hagiwara, Gyeong Moon Kim, A. Barchielli, Ingegerd Söderström, M. Uguccioni, Peter Crome, Laurent Derex, Yasushi Okada, Magnus Strand, Parisa Hasanzadeh, Lars Weinehall, Guy Louis-Tisserand, Alireza Khosravi, Simona Fanucchi, Alberto Chiti, S. Giampaoli, Jung Han Yoon, Nicola Morelli, Per-Gunnar Wiklund, Akira Munakata, Norihito Shimamura, Tooru Inoue, Joseph Ngeh, Göran Hallmans, Marlène Wiart, Sa Rah Yoon, Virginie Desestret, C Sonnoli, Jérôme Honnorat, Kazunori Toyoda, Setsuro Ibayashi, P. Spolaore, Tommy Olsson, E. de Campora, Giovanni Orlandi, P. Ciccarelli, C.A. Goldoni, Norbert Nighoghossian, D. Vanuzzo, Khalid Ali, and S. Cakmak

Subjects
geography, medicine.medical_specialty, Summit, geography.geographical_feature_category, Neurology, business.industry, Family medicine, Medicine, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, medicine.disease, Stroke
Published
2007
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37. Contents Vol. 24, 2007

Author

E. de Campora, Giovanni Orlandi, Chin Sang Chung, Christine Roffe, Karel Fuentes, G. Cesana, Virginie Desestret, Göran Hallmans, Lars Weinehall, C Sonnoli, Yves Berthezène, Joseph Ngeh, Jérôme Honnorat, Alireza Khosravi, Diosely C. Silveira, Parisa Hasanzadeh, Seung Hyeon Yeo, Kwang Ho Lee, Guy Louis-Tisserand, Nicola Morelli, Per-Gunnar Wiklund, Stefan Söderberg, Gyeong Moon Kim, Hiroki Ohkuma, Elizabeth Cheek, P. Spolaore, L. Palmieri, Marc Hermier, Shidokht Hosseini, Oh Young Bang, Sandeep Gupta, Sheila Sills, Tommy Olsson, Magnus Strand, Noriko Hagiwara, Jean-Claude Froment, Nikolaos I.H. Papamitsakis, Peter Crome, Laurent Derex, Tooru Inoue, Yasushi Okada, Tae-Hee Cho, Nizal Sarrafzadegan, F. Vancheri, Elisa Giorli, Akira Munakata, S. Giampaoli, P. Ciccarelli, Norihito Shimamura, A. Barchielli, M. Uguccioni, Jung Han Yoon, Simona Fanucchi, Kazunori Toyoda, Rina Torisu, Allan Hackshaw, Jung Im Seok, Setsuro Ibayashi, C.A. Goldoni, Marlène Wiart, Kotaro Yasumori, Takahiro Nakano, Sa Rah Yoon, Shahram Oveisgharan, S. Cakmak, Norbert Nighoghossian, Ingegerd Söderström, D. Vanuzzo, Khalid Ali, Seung Soo Sheen, Alberto Chiti, and Shahin Shirani

Subjects
Neurology, Traditional medicine, business.industry, Medicine, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Published
2007
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38. Polymorphisms at the Osteoprotegerin and Interleukin-6 Genes in Relation to First-Ever Stroke

Author

Göran Hallmans, Ingegerd Söderström, Stefan Söderberg, Lars Weinehall, Magnus Strand, Per-Gunnar Wiklund, and Tommy Olsson

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Osteoporosis, Polymorphism, Single Nucleotide, Risk Assessment, Brain Ischemia, Gene Frequency, Osteoprotegerin, Risk Factors, Internal medicine, Odds Ratio, medicine, Humans, Genetic Predisposition to Disease, First ever stroke, Prospective Studies, Interleukin 6, Aged, Cerebral Hemorrhage, Sweden, Intracerebral hemorrhage, Postmenopausal women, biology, Interleukin-6, business.industry, Middle Aged, medicine.disease, Health Surveys, Stroke, Arterial calcification, Logistic Models, Endocrinology, Increased risk, Neurology, Case-Control Studies, biology.protein, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Abstract

Background: Arterial calcification and osteoporosis often coexist, especially in postmenopausal women. Osteoporosis associates with a substantially increased risk of stroke in elderly women, suggesting that impaired estrogen signaling may link stroke and osteoporosis. Osteoprotegerin (OPG, TNFRSF11B) and interleukin-6 (IL-6, IL6) are putative target genes for estrogen signaling and have been implicated in both cardiovascular diseases and osteoporosis. We hypothesized that specific polymorphisms in these genes may be associated with increased risk of ischemic stroke or intracerebral hemorrhage (ICH). Methods: We performed a population-based prospective nested case-control study, in which the relationships between polymorphisms (OPG-1181G/C, OPG-950T/C and IL6-174G/C) and ischemic stroke and ICH were examined. Definitive first-ever stroke events (n = 388), i.e. ischemic stroke (n = 320), ICH (n = 61) and unspecified stroke (n = 7) cases, and controls without cardiovascular disease (n = 773), matched for age, sex and geographical region were studied. Univariate and multivariate models using conditional logistic regression, which included traditional risk factors, were used to test for association. Results: Carriers of the OPG-1181C/C genotype had a significantly (p = 0.018) increased risk of ICH (OR, 2.69; 95% CI, 1.19–6.12) in the univariate analysis. After adjustments (hypertension, diabetes, BMI and triglycerides), this genotype remained significantly (p = 0.005) associated with ICH (OR, 6.04; 95% CI, 1.71–21.29). By contrast, no correlations were found between this genotype and ischemic stroke, nor between the OPG-950T/C or IL6-174G/C polymorphisms and stroke subtypes. Conclusions: In this population, the OPG-1181C/C genotype associates with first-ever ICH, implying that alterations in OPG-mediated signaling in the vasculature may be involved in the pathophysiology of this disease.

Published
2007
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39. Estrogen Receptor Alpha Gene Polymorphisms and First-Ever Intracerebral Hemorrhage

Author

Magnus Strand, Per-Gunnar Wiklund, Lars Weinehall, Göran Hallmans, Tommy Olsson, Stefan Söderberg, and Ingegerd Söderström

Subjects
Male, Heterozygote, medicine.medical_specialty, Genotype, Molecular Sequence Data, Blood Pressure, Vasodilation, Brain Ischemia, Estrogen-related receptor alpha, Gene Frequency, Polymorphism (computer science), Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Prospective Studies, Stroke, Gene, Estrogen receptor beta, Aged, Cerebral Hemorrhage, Intracerebral hemorrhage, Polymorphism, Genetic, Base Sequence, business.industry, Estrogen Receptor alpha, Middle Aged, medicine.disease, Endocrinology, Neurology, Case-Control Studies, Hypertension, Female, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Estrogen receptor alpha
Abstract

Background: Signaling through estrogen receptor alpha (ERα) regulates vasodilatation and atherogenesis. Since hypertension and atherosclerosis are major mechanisms in stroke development, we hypothesized that genetic variants of the ERα gene (ESR1) are determinants of future ischemic stroke or intracerebral hemorrhage (ICH). Methods: In a population-based prospective nested case-control study, the relationships between ESR1 polymorphisms (c.454–397T>C and c.454–351A>G) and ischemic stroke and ICH were examined in univariate and multivariate models using conditional logistic regression, which included established risk factors.Definitive first-ever stroke events (n = 388), including ischemic stroke (n = 320), ICH (n = 61), and unspecified stroke (n = 7) cases, and controls without cardiovascular disease (n = 773), matched for age, sex, and geographical region were included. Results: Carriers of the c.454–397T/T genotype had a significantly (p = 0.017) increased risk of ICH (OR 2.31, 95% CI 1.16–4.60) in a univariate analysis. This association persisted (OR 3.94, 95% CI 1.54–10.03), after adjustment for stroke risk determinants. Carriers of c.454–397T/T or c.454–397T/C genotypeshad significantly (p = 0.002 and p = 0.004, respectively) higher mean systolic blood pressure (SBP), than carriers of c.454–397C/C, and a similar relationship was observed for diastolic blood pressure (DBP). The combinations of c.454–397T/T genotype and hypertension (OR 21.46, 95% CI 5.20–88.51), or high SBP (OR 18.17, 95% CI 4.91–67.31) or DBP (OR 11.94, 95% CI 3.75–38.03), were strongly associated with increased risk of ICH. Conclusions: In this population,the c.454–397T/T genotype associates with first-ever ICH, particularly in combination with hypertension. This implies that alterations in ERα-mediated signaling may be involved in the pathophysiology of this disease, with a putative impact on primary prevention.

Published
2007
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40. Harmonising EU Competition Litigation : The New Directive and Beyond

Author

Bergström, Maria, Marios, Iacovides, Magnus, Strand, Bergström, Maria, Marios, Iacovides, and Magnus, Strand

Abstract

This volume in the Swedish Studies in European Law series, produced by the Swedish Network for European Legal Studies, heralds the new harmonized regime of private enforcement of EU competition law. In 2013, the Commission issued a communication and practical guide to the quantification of harm in antitrust litigation and a recommendation on collective redress. In 2014, the long-awaited Directive on actions for damages for infringements of EU competition law was finally adopted. In 2016, the Commission is expected to issue guidelines on the passing-on of overcharges. This book examines these recent developments and offers the perspectives of judges, officials, practitioners and academics. With a preface by Judge Carl Wetter of the General Court, the book explores five different themes. Section one presents the main policy issues and challenges. In section two, the new regime is placed in the bigger picture of recent EU law developments. In section three, the nexus between private enforcement and transparency is investigated. A comparative perspective is offered in section four, by looking into private enforcement in five Member State jurisdictions. Finally, issues relating to causation, harm and indirect purchasers are explored in section five.

Published
2016

41. Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy

Author

Marie Cohen, Olga Nagaeva, Gabriela Barrientos, Irene Tirado-González, Lucia Mincheva-Nilsson, Valerie Shaikly, Lennart Kjellberg, Magnus Strand, Nancy Freitag, Burghard F. Klapp, and Sandra M. Blois

Subjects
Isoantigens, Embryology, Galectin 1, Placenta, HLA-G, Gene Expression, gal-1, Immune tolerance, Pregnancy, Galectin-1, Protein Isoforms, reproductive and urinary physiology, ddc:618, Decidua, Trophoblast, Obstetrics and Gynecology, purl.org/becyt/ford/3.1 [https], Prognosis, Trophoblasts, Medicina Básica, medicine.anatomical_structure, embryonic structures, Female, purl.org/becyt/ford/3 [https], Adult, CIENCIAS MÉDICAS Y DE LA SALUD, Inmunología, Human leukocyte antigen, Biology, Cell Line, Andrology, Immune system, Cell Adhesion, Immune Tolerance, Genetics, medicine, Humans, Human embryo, Embryo Implantation, Molecular Biology, Immune Evasion, Spontaneous abortion, HLA-G Antigens, Cell Biology, Abortion, Spontaneous, Pregnancy Trimester, First, Blastocyst, Reproductive Medicine, Immunology, Predictive factor, Biomarkers, Developmental Biology
Abstract

Galectin-1 (gal-1) is expressed at the feto-maternal interface and plays a role in regulating the maternal immune response against placental alloantigens, contributing to pregnancy maintenance. Both decidua and placenta contribute to gal-1 expression and may be important for the maternal immune regulation. The expression of gal-1 within the placenta is considered relevant to cell-adhesion and invasion of trophoblasts, but the role of gal-1 in the immune evasion machinery exhibited by trophoblast cells remains to be elucidated. In this study, we analyzed gal-1 expression in preimplantation human embryos and first-trimester decidua-placenta specimens and serum gal-1 levels to investigate the physiological role played by this lectin during pregnancy. The effect on human leukocyte antigen G (HLAG) expression in response to stimulation or silencing of gal-1 was also determined in the human invasive, proliferative extravillous cytotrophoblast 65 (HIPEC65) cell line. Compared with normal pregnant women, circulating gal-1 levels were significantly decreased in patients who subsequently suffered a miscarriage. Human embryos undergoing preimplantation development expressed gal-1 on the trophectoderm and inner cell mass. Furthermore, our in vitro experiments showed that exogenous gal-1 positively regulated the membrane-bound HLA-G isoforms (HLA-G1 and G2) in HIPEC65 cells, whereas endogenous gal-1 also induced expression of the soluble isoforms (HLA-G5 and -G6). Our results suggest that gal-1 plays a key role in pregnancy maternal immune regulation by modulating HLA-G expression on trophoblast cells. Circulating gal-1 levels could serve as a predictive factor for pregnancy success in early human gestation. Fil: Tirado González, Irene. Medicine University Berlin; Alemania Fil: Freitag, Nancy. Medicine University Berlin; Alemania Fil: Barrientos, Gabriela Laura. Medicine University Berlin; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Shaikly, Valerie. University Of Essex; Reino Unido. Assisted Reproduction and Gynaecology Centre; Reino Unido Fil: Nagaeva, Olga. Universidad de Umea; Suecia Fil: Strand, Magnus. Universidad de Umea; Suecia Fil: Kjellberg, Lennart. Universidad de Umea; Suecia Fil: Klapp, Burghard F.. Medicine University Berlin; Alemania Fil: Mincheva Nilsson, Lucia. Universidad de Umea; Suecia Fil: Cohen, Marie. Laboratoire d’Hormonologie; Suiza Fil: Blois, Sandra M.. Medicine University Berlin; Alemania

Published
2013
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42. Maternal Foxp3 expressing CD4+ CD25+ and CD4+ CD25- regulatory T-cell populations are enriched in human early normal pregnancy decidua: a phenotypic study of paired decidual and peripheral blood samples

Author

Tanya, Dimova, Olga, Nagaeva, Ann-Christin, Stenqvist, Malin, Hedlund, Lennart, Kjellberg, Magnus, Strand, Eva, Dehlin, and Lucia, Mincheva-Nilsson

Subjects
CD4-Positive T-Lymphocytes, Transforming Growth Factor beta1, Phenotype, Antigens, CD, Pregnancy, Decidua, Cytokines, Humans, Female, Forkhead Transcription Factors, OX40 Ligand, T-Lymphocytes, Regulatory, Neuropilin-1
Abstract

Regulatory T cells (Treg cells), a small subset of CD4(+) T cells maintaining tolerance by immunosuppression, are proposed contributors to the survival of the fetal semiallograft. We investigated Treg cells in paired decidual and peripheral blood (PB) samples from healthy women in early pregnancy and PB samples from non-pregnant women.Distribution, location, cytokine mRNA, and phenotype were assessed in CD4(+) CD25(+) Treg cells from paired samples using immunohistochemistry, immunofluorescence, flow cytometry, and real-time quantitative RT-PCR.The presence and in situ distribution of CD4(+) Foxp3(+) Treg cells in decidua are hereby demonstrated for the first time. Three Foxp3(+) cell populations, CD4(+) CD25(++) Foxp3(+), CD4(+) CD25(+) Foxp3(+), and CD4(+) CD25(-) Foxp3(+), were enriched locally in decidua. In contrast, no statistically significant difference in numbers of circulating Treg cells between pregnant and non-pregnant women was found. The Foxp3(+) cells expressed the surface molecules CD45RO, CTLA-4, CD103, Neuropilin-1, LAG-3, CD62L, and TGFβ1 mRNA consistent with Treg phenotype. The population of CD4(+) CD25(-) Foxp3(+) cells, not described in human decidua before, was enriched 10-fold compared with PB in paired samples. Their cytokine expression was often similar to Th3 profile, and the Foxp3 mRNA expression level in CD4(+) CD25(-) cells was stable and comparable to that of CD4(+) CD25(+) Treg cells implying that the majority of CD4(+) CD25(-) Foxp3(+) cells might be naïve Treg cells.(i) There is a local enrichment of Treg cells in decidua (ii) The exclusive accumulation of decidual CD4(+) CD25(-) Foxp3(+) cells suggests an additional reservoir of Foxp3(+) naïve Treg cells that can be converted to 'classical' Treg cells in uterus.

Published
2011

43. Det konsosierte demokratiet i Nederland og Østerrike : En analyse av de demokratiske endringene fra 60-tallet til i dag

Author

Hauge, Magnus Strand

Abstract

Det har blitt hevdet at det konsosierte demokratiet har vært på tilbakegang i Nederland og Østerrike siden 60-tallet. I denne oppgaven analyseres denne endringen med Lijpharts demokratitypologi som utgangspunkt. De konsosierte landene er kjennetegnet ved en heterogen politisk kultur og en samarbeidende eliteatferd. Det blir funnet endringer i begge variablene både i Nederland og Østerrike. Ingen av landene kan regnes som konsosierte lenger. I dag passer de bedre inn i kategorien sentripetalt demokrati. Ved å se på endringene i den politiske kulturen og eliteatferden over tid, har det vært mulig å avdekke kausalmekanismene mellom disse to variablene. Mens endringene i den politiske kulturen i stor grad har påvirket eliteatferden direkte i Nederland, har denne påvirkningen nesten utelukkende vært indirekte i Østerrike. Her har framveksten av protestpartier (først og fremst FPÖ) påvirket de konsosierte ordningene. I en sammenlikning av landene peker jeg på partienes styrke innenfor subkulturene som en viktig årsak til denne forskjellen.

Published
2011

44. 17beta-estradiol and enriched environment accelerate cognitive recovery after focal brain ischemia

Author

Magnus Strand, Tommy Olsson, Salmir Nasic, Ingegerd Söderström, and Anna-Cajsa Ingridsson

Subjects
Brain Infarction, medicine.medical_specialty, Neurology, Time Factors, medicine.drug_class, Ovariectomy, Sensation, Hippocampus, Environment, Motor Activity, Neuropsychological Tests, Functional Laterality, Brain Ischemia, Brain ischemia, Rats, Sprague-Dawley, medicine, Reaction Time, Animals, Early Growth Response Protein 1, Environmental enrichment, Analysis of Variance, Estradiol, General Neuroscience, Cognition, Estrogens, Recovery of Function, medicine.disease, Rats, Disease Models, Animal, Gene Expression Regulation, Estrogen, Vibrissae, Ischemic stroke, Female, Psychology, Cognition Disorders, Neuroscience, Psychomotor Performance
Abstract

Cognitive impairments, including spatial memory and learning deficiencies, are common after ischemic stroke. Estrogen substitution improves cognitive functions in post-menopausal women and ovariectomized rodents, partially through induction of neuroplasticity in the hippocampal formation. Post-ischemic housing of male rats in an enriched environment (EE) improves functional outcome, without changing infarct volume. We hypothesized that 17beta-estradiol combined with an EE would accelerate cognitive recovery after focal brain ischemia in ovariectomized rats and that recovery would be related to altered expression of nerve growth factor-induced gene (NGFI)-A in the hippocampus. 17beta-estradiol or placebo pellets were implanted 6 h after transient middle cerebral artery occlusion. Two days later, rats were placed in an EE or a deprived environment (DE) for 6 weeks. At 5 weeks after middle cerebral artery occlusion, 17beta-estradiol-treated rats housed in an EE showed improvements in cognitive function (i.e. shorter latency and path in the Morris water maze task) compared with placebo-treated animals housed in an EE. Furthermore, beneficial effects on latency and path were observed when comparing EE-housed vs. DE-housed 17beta-estradiol-treated rats. When comparing 17beta-estradiol-treated EE-housed rats vs. placebo-treated DE-housed rats, pronounced effects on latency and path were observed. Infarct volumes did not differ between groups. 17beta-estradiol-treated EE-housed rats had significantly higher NGFI-A mRNA expression bilaterally in the cornu ammonis 1 region and in the ipsilateral dentate gyrus of the hippocampus, compared with placebo-treated EE-housed rats. In conclusion, 17beta-estradiol treatment combined with an EE improved recovery of cognitive function after experimental brain ischemia, putatively through the upregulation of NGFI-A in hippocampal subregions.

Published
2009

45. Intra-adipose sex steroid metabolism and body fat distribution in idiopathic human obesity

Author

Magnus Strand, Ruth Andrew, Dawn E W Livingstone, Brian R. Walker, Hannele Yki-Järvinen, Stefan Söderberg, Jukka Westerbacka, Deborah Wake, Tommy Olsson, and Eva Rask

Subjects
Adult, Male, medicine.medical_specialty, 3-Hydroxysteroid Dehydrogenases, Endocrinology, Diabetes and Metabolism, Biopsy, Adipose tissue, 030209 endocrinology & metabolism, Biology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Waist–hip ratio, Aromatase, Sex Factors, Internal medicine, medicine, Distribution (pharmacology), Body Fat Distribution, Humans, Obesity, RNA, Messenger, Gonadal Steroid Hormones, 030304 developmental biology, Body fat distribution, Aged, 2. Zero hunger, 0303 health sciences, medicine.diagnostic_test, Reverse Transcriptase Polymerase Chain Reaction, Waist-Hip Ratio, Aldo-Keto Reductase Family 1 Member C3, Estrogen Receptor alpha, Hydroxysteroid Dehydrogenases, Metabolism, Middle Aged, medicine.disease, Subcutaneous Fat, Abdominal, Plethysmography, Cross-Sectional Studies, Sex steroid, Receptors, Androgen, Hydroxyprostaglandin Dehydrogenases, Regression Analysis, Female
Abstract

Causes of visceral fat accumulation include glucocorticoid excess or decreased oestrogen/androgen ratio either in plasma or within adipose tissue. In obese subjects, the intra-adipose cortisol-generating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is increased, but information on sex steroid signalling is sparse. We aimed to test associations between body fat or fat distribution and mRNA transcript levels for androgen and oestrogen receptors and for enzymes metabolizing sex steroids in adipose tissue.A cross-sectional study.Forty-five healthy men and women with body mass index (BMI) 21-36 kg/m(2).In subcutaneous adipose biopsies we measured mRNAs for enzymes metabolizing local oestrogens (aromatase) and androgens [5alpha-reductase type 1; AKR1C2 (3alpha-HSD3); AKR1C3 (17beta-HSD5, 3alpha-HSD2)] and for sex steroid receptors [oestrogen receptor (ER)-alpha and androgen receptor (AR)]. We related these to body fat mass and distribution.Generalized obesity (BMI) was associated with increased aromatase mRNA (r = 0.35, P0.05). Central obesity (waist : hip ratio) was associated with mRNA for AKR1C2 (r = 0.28, P0.05) and AKR1C3 (r = 0.38, P0.01) but not aromatase (r = 0.06). 5alpha-Reductase type 1, ER and AR mRNA levels did not predict fat amount or its distribution.These data on transcript levels suggest that, in idiopathic obesity, increased intra-adipose oestrogen generation by aromatase predicts peripheral fat distribution, while androgen metabolism by AKR1C isoforms predicts central fat distribution, supporting the hypothesis that intra-adipose sex steroid metabolism is a determinant of gynoid vs. android patterns of body fat.

Published
2007

46. An amphipathic peptide with antibiotic activity against multidrug-resistant Gram-negative bacteria

Author

Alysha G. Elliott, Johnny X. Huang, Søren Neve, Johannes Zuegg, Ingrid A. Edwards, Amy K. Cain, Christine J. Boinett, Lars Barquist, Carina Vingsbo Lundberg, Jason Steen, Mark S. Butler, Mehdi Mobli, Kaela M. Porter, Mark A. T. Blaskovich, Sergio Lociuro, Magnus Strandh, and Matthew A. Cooper

Subjects
Science
Abstract

Peptide antibiotics often display a very narrow therapeutic index. Here, the authors present an optimized peptide antibiotic with broad-spectrum in vitro activities, in vivo efficacy in multiple disease models against multidrug-resistant Gram-negative infections, and reduced toxicity.

Published
2020
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47. Subject Index Vol. 24, 2007

Author

Jean-Claude Froment, Nikolaos I.H. Papamitsakis, Simona Fanucchi, Elisa Giorli, Hiroki Ohkuma, Yasushi Okada, P. Ciccarelli, Yves Berthezène, Elizabeth Cheek, Ingegerd Söderström, Oh Young Bang, Kwang Ho Lee, Virginie Desestret, C Sonnoli, Jérôme Honnorat, Stefan Söderberg, Marlène Wiart, Tae-Hee Cho, Rina Torisu, Seung Hyeon Yeo, L. Palmieri, Noriko Hagiwara, Nizal Sarrafzadegan, A. Barchielli, Parisa Hasanzadeh, Guy Louis-Tisserand, Chin Sang Chung, M. Uguccioni, Kazunori Toyoda, Lars Weinehall, Karel Fuentes, Sa Rah Yoon, Norihito Shimamura, Sandeep Gupta, S. Cakmak, Kotaro Yasumori, Alireza Khosravi, C.A. Goldoni, Takahiro Nakano, Alberto Chiti, Göran Hallmans, Seung Soo Sheen, Marc Hermier, Peter Crome, Joseph Ngeh, Diosely C. Silveira, Gyeong Moon Kim, Shahin Shirani, Norbert Nighoghossian, Tooru Inoue, Magnus Strand, E. de Campora, Giovanni Orlandi, D. Vanuzzo, Sheila Sills, F. Vancheri, Nicola Morelli, Per-Gunnar Wiklund, Shahram Oveisgharan, P. Spolaore, Khalid Ali, Allan Hackshaw, Tommy Olsson, Christine Roffe, Setsuro Ibayashi, G. Cesana, Akira Munakata, S. Giampaoli, Jung Han Yoon, Shidokht Hosseini, Laurent Derex, and Jung Im Seok

Subjects
Index (economics), Neurology, business.industry, Statistics, Medicine, Subject (documents), Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Published
2007
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48. Abstract C140: RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and ovarian cancer

Author

Stefan Bentink, Xandra O. Breakefield, Eva Lundin, Leonara Balaj, Dima Ter-Ovanesyan, Fred H. Hochberg, Ulrika Ottander, Tobias Limperg, Lin Dan Zhu, Afshin Salehi, Bob S. Carter, Nina Ohlson, Mikkel Noerholm, Magnus Strand, and Johan Skog

Subjects
Cancer Research, Microarray analysis techniques, Microvesicle, RNA, Biology, Bioinformatics, medicine.disease, Microvesicles, Oncology, Gene expression, Cancer research, medicine, Neoplastic transformation, Ovarian cancer, Gene
Abstract

Background: Recent studies have shown that RNA isolated from exosomes and other microvesicles (exoRNA) contain diagnostically relevant transcripts of tumor origin. In this study we sought to identify specific biomarkers of glioblastoma multiforme (GBM) and malignant ovarian cancer in the ribonucleic acid fraction extracted from microvesicles (exoRNA) isolated from the serum of affected patients. Methods: All samples were collected following informed consent in accordance with the appropriate protocols approved by the MGH Institutional Review Board (GBM) and the Umeå University ethics committee (ovarian tumors). Patients with primary GBM (N=9), normal controls (N=7); and pathologically proven benign (N=16), borderline (N=19), and malignant (N=29, stage I-IV, grade 1–3) neoplastic transformation of the ovaries were included. ExoRNA isolated from patient serum was amplified and analyzed by microarray analysis on Agilent 4×44K arrays (GBM) and Agilent 8×60K arrays (ovarian tumors). Differential expressions between control and GBM samples were validated by qRT-PCR in a separate set of samples (N=10 in both groups). Results: Array analysis of the amplified exoRNA yielded significant signals from at least 10,000 genes on the array for all samples. The expression profiles of the exoRNA from GBM patients were shown to be different from those of normal healthy volunteers. The most significant expression differences observed in the array analysis pertained to down-regulated genes (121 genes >2-fold down) in the GBM patient exoRNA, which was validated by qRT-PCR on several genes. Gene ontology analysis of the down-regulated genes indicated these are primarily mRNAs coding for ribosomal proteins and other genes related to ribosome production. Supervised analysis showed no significant differential gene expression between the benign, borderline, and malignant ovarian tumors. However, unsupervised Consensus Clustering yielded a clear segregation of the patients into two new groups (100% resampling consensus for 61 samples). Gene Set Enrichment Analysis (GSEA) showed a strong association of one of the two groups with genes linked to translation initiation (FDR q-value 0.04), and mRNA processing (FDR q-value 0.032). GSEA also confirmed a strong overlap of the genes separating the ovarian cancer samples into two groups with those discriminating GBM from healthy control individuals. Conclusions: Microvesicle isolated RNA from patients with GBM is significantly different from that of normal control individuals. The same genes support a binary classification of ovarian tumors suggesting that common biological processes may be in effect for these different tumor types. The common signature is hallmarked by messenger RNAs coding for ribosome production, which are significantly downregulated in GBM exoRNA and in one of two novel subgroups of ovarian tumors. While the biological role of this signature remains to be elucidated, we conclude that exosomal RNA expression profiling has the potential to serve as a clinically relevant diagnostic source of information about the biology, malignancy, and state of tumors. This underlines the diagnostic potential of exosomes not only in early diagnosis, but also in directing therapies, evaluating response and in situations where biopsy samples are difficult to access. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C140.

Published
2011
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49. Synergistic Effect of Combinations Containing EDTA and the Antimicrobial Peptide AA230, an Arenicin-3 Derivative, on Gram-Negative Bacteria

Author

Anita Umerska, Magnus Strandh, Viviane Cassisa, Nada Matougui, Matthieu Eveillard, and Patrick Saulnier

Subjects
antimicrobial peptides, synergy, arenicin, EDTA, gram-negative bacteria, antibiotic resistance, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, ESKAPE pathogens, Microbiology, QR1-502
Abstract

The worldwide occurrence of resistance to standard antibiotics and lack of new antibacterial drugs demand new strategies to treat complicated infections. Hence, the aim of this study was to examine the antibacterial activities of an antimicrobial peptide, arenicin-3 derivative AA230, and ethylenediaminetetraacetic acid (EDTA) as well as the two compounds in combination against Gram-negative bacteria. AA230 showed strong antibacterial activity against all of the studied standard strains and clinical isolates, with minimum inhibitory concentrations ranging between 1 µg/mL and 8 µg/mL. AA230 exhibited a bactericidal mode of action. EDTA inhibited the growth of Acinetobacter baumannii at 500⁻1000 µg/mL. Strains of Acinetobacter baumannii were found to be more susceptible to EDTA than Pseudomonas aeruginosa or Escherichia coli. The antibacterial effects of both AA230 and EDTA were independent of the antibiotic resistance patterns. Indifference to synergistic activity was observed for AA230 and EDTA combinations using checkerboard titration. In time-kill studies, a substantial synergistic interaction between AA230 and EDTA was detected against all of the tested strains. The addition of EDTA enabled a 2⁻4-fold decrease in the AA230 dose. In conclusion, AA230 could have potential applications in the treatment of infections caused by Gram-negative organisms, and its effect can be potentiated by EDTA.

Published
2018
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50. Novel staphylococcal glycosyltransferases SdgA and SdgB mediate immunogenicity and protection of virulence-associated cell wall proteins.

Author

Wouter L W Hazenbos, Kimberly K Kajihara, Richard Vandlen, J Hiroshi Morisaki, Sophie M Lehar, Mark J Kwakkenbos, Tim Beaumont, Arjen Q Bakker, Qui Phung, Lee R Swem, Satish Ramakrishnan, Janice Kim, Min Xu, Ishita M Shah, Binh An Diep, Tao Sai, Andrew Sebrell, Yana Khalfin, Angela Oh, Chris Koth, S Jack Lin, Byoung-Chul Lee, Magnus Strandh, Klaus Koefoed, Peter S Andersen, Hergen Spits, Eric J Brown, Man-Wah Tan, and Sanjeev Mariathasan

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Infection of host tissues by Staphylococcus aureus and S. epidermidis requires an unusual family of staphylococcal adhesive proteins that contain long stretches of serine-aspartate dipeptide-repeats (SDR). The prototype member of this family is clumping factor A (ClfA), a key virulence factor that mediates adhesion to host tissues by binding to extracellular matrix proteins such as fibrinogen. However, the biological siginificance of the SDR-domain and its implication for pathogenesis remain poorly understood. Here, we identified two novel bacterial glycosyltransferases, SdgA and SdgB, which modify all SDR-proteins in these two bacterial species. Genetic and biochemical data demonstrated that these two glycosyltransferases directly bind and covalently link N-acetylglucosamine (GlcNAc) moieties to the SDR-domain in a step-wise manner, with SdgB appending the sugar residues proximal to the target Ser-Asp repeats, followed by additional modification by SdgA. GlcNAc-modification of SDR-proteins by SdgB creates an immunodominant epitope for highly opsonic human antibodies, which represent up to 1% of total human IgG. Deletion of these glycosyltransferases renders SDR-proteins vulnerable to proteolysis by human neutrophil-derived cathepsin G. Thus, SdgA and SdgB glycosylate staphylococcal SDR-proteins, which protects them against host proteolytic activity, and yet generates major eptopes for the human anti-staphylococcal antibody response, which may represent an ongoing competition between host and pathogen.

Published
2013
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